Revision as of 19:27, 25 July 2020

Patients with solid tumors that have HER2 overexpression, amplification, or HER2-activating mutation as identified by assays performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
- Assays using in situ hybridization (fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) must indicate the presence of gene amplification with a HER2/CEP17 ratio of ≥ 2.0 or HER2 gene copy number > 6.0.
- Assays using IHC must indicate a score of 3 +.
- Assays using next generation sequencing (NGS) of genes with known or potentially clinically relevant alterations or analysis by real-time polymerase chain reaction (RT-PCR) must identify clinically activating mutations (those with major coding disruptions resulting in an amino acid change that is likely to be detrimental to protein function, including premature stop codons or frameshift mutations early in the coding region) or copy number gain.
- In cases where multiple assays are done, HER2 positivity by any of the testing methodologies would make the patient eligible as long as eligibility criteria are fulfilled.

Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

MyPathway: Meric-Bernstam F, Hurwitz H, Raghav KPS, MCwilliams RR, Fakih M, VanderWalde A, Swanton C, Kurzrock R, Burris H, Sweeney C, Bose R, Spigel DR, Beattie MS, Blotner S, Stone A, Schulze K, Cuchelkar V, Hainsworth J. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019 Apr;20(4):518-530. Epub 2019 Mar 8. link to original article contains verified protocol PubMed

Lapatinib & Trastuzumab

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Study	Evidence	Efficacy
Sartore-Bianchi et al. 2016 (HERACLES)	Phase II	ORR: 30% (95% CI 14-50%)

Patients enrolled in HERACLES had ECOG 0-1

Diagnostic criteria for Her2 positivity in HERACLES:

or

2+ HER2 score and a HER2:CEP17 ratio higher than two in more than 50% of cells by FISH

Lapatinib (Tykerb) 1000 mg PO once per day
Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1
- Cycle 2 onwards: 2 mg/kg IV once on day 1

7-day cycles

HERACLES: Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Jun;17(6):738-746. Epub 2016 Apr 20. link to original article PubMed

@@ Line 60: / Line 60: @@
 |-
 |}
-'''Biomarker eligibility criteria'''
+====Biomarker eligibility criteria====
-HER2 amplification
+*HER2 amplification
 ''Patients enrolled in MyPathway had ECOG 0-2''
@@ Line 74: / Line 74: @@
 **In cases where multiple assays are done, HER2 positivity by any of the testing methodologies would make the patient eligible as long as eligibility criteria are fulfilled.
-====Chemotherapy====
+====Targeted therapy====
 *[[Pertuzumab (Perjeta)]] as follows:
@@ Line 106: / Line 106: @@
 |-
 |}
-'''Biomarker eligibility criteria'''
+====Biomarker eligibility criteria====
-KRAS wild-type, HER2 amplification
+*KRAS wild-type, HER2 amplification
 ''Patients enrolled in HERACLES had ECOG 0-1''
@@ Line 120: / Line 120: @@
 *2+ HER2 score and a HER2:CEP17 ratio higher than two in more than 50% of cells by FISH
-====Chemotherapy====
+====Targeted therapy====
 *[[Lapatinib (Tykerb)]] 1000 mg PO once per day